Thousands of biological research and development facilities worldwide deal with some aspect of the growth and division of cells. Suspensions of minimally disturbed newborn cells are valuable for analysis of the cell cycle, including analysis of all mammalian cell types. The newborn cell suspensions can be used to analyze cell cycle gene expression in mammalian cells, such as hematopoietic cells. Growing and dividing cells are used in basic research, drug development and testing, and bio-product manufacturing, for example.
Furthermore, during the past few years there has been a significant expansion in research in the related areas of cell cycle regulation, cell senescence, apoptosis, and cellular differentiation. Studies related to these specific areas require access to, and reliable production of, large quantities of cells that are at a specific, known phase of growth and division, such as a particular stage in the cell cycle, and state of senescence.
Obtaining adequate quantities of synchronous cells whose physiology is minimally disturbed, is not an easy task. This is because contemporary production methods expose cells to metabolic disturbances, such as with the addition of drugs or deprivation of nutrients, in order to obtain an exponentially growing culture of cells, where the population is distributed throughout all phases of the cell cycle, to become growth inhibited at a particular stage in the cell cycle. Even if these methods are successful, it is unclear if these cellular events represent the true “steady state” of the cells, where all biochemical and metabolic processes are in balance or an artifact created by the disturbance.
Attempts have been made to produce devices and methods for manufacturing large quantities of cells that are at specific stages in cell cycles and senescence. For example, U.S. Pat. No. 6,001,642 (Tsao) and U.S. Pat. No. 5,153,131 (Wolf) are directed to bioreactors that grow cells in suspension or are attached to a substrate for three-dimensional tissue or organ growth. However, while these devices generated cells, they did not generate newborn cells and could not continuously generate cells.